Studies of the regulation of lipid metabolism in cultured human macrophages derived from circulating monocytes will be carried out by varying the culture medium and using radiolabeled compounds to measure synthesis and degradation. A comparison between a short term culture period (72-96 hours) and a longer period (10-12 days) reveals differences in the nature of cellular regulation of lipoprotein uptake and sterol synthesis. These observations are pertinent to the problem of the existence of a specific high affinity receptor for LDL in the long lived macrophage grown in deprived medium. Such a receptor is not apparent in the freshly obtained monocyte, or such cells grown for a short time interval. Under all conditions of study, the content of esterified cholesterol is of low magnitude, due to low activity of the cholesterol-esterifying enzyme (ACAT), and vigorous activity of cholesterol ester hydrolase. It should be noted that atheromatous lesions have a considerable content of cholesterol ester, and that macrophages are recognized to have an important role in the genesis of such lesions. The in vitro study of cultured macrophages should provide insight into the in vivo mechanisms. Our published method for detecting very small quantities of tocopherol (less than 1 ng) uses high performance liquid chromatography and fluorescence spectrophotometry. Levels in premature infants suffering from hemolytic anemia or respiratory distress syndrome are easily obtained. The method also permits the measurement of the exchange of tocopherol prophylactic role of tocopherol during cancer chemotherapy with adriamycin is under investigation.